Phorboxazole A is an interesting new natural product that shows remarkable anticancer activity. In tests against the NCI's panel tumor cell lines it was found, for example, to inhibit the growth of colon tumor cells HCT-116 with a GI50 of 4.36 X 10-10 M. Such exceptional potency against human solid tumors is comparable with the most potent agents known to date, and makes the synthesis of phorboxazole A a high priority in the development of new anticancer agents. Phorboxazole A and B were isolated from a marine sponge, Phorbos sp. in 0.040 percent and 0.017 percent of the dry weight, which provided enough material for structure determination and initial biological evaluation, but will not support extensive anticancer evaluation or the preparation of structural analogs. Further progress in the evaluation of phorboxazole A and its analogs for cancer chemotherapy will depend upon the development of effective routes for its total synthesis. We propose a highly convergent synthesis of phorboxazole using our newly discovered reductive acetylation and Prins cyclization of an ester to give a tetrahydropyran stereoselectively. The scope of this reaction will be investigated, and two of the tetrahydropyran rings in the phorboxazoles will be prepared using this method. The side chain A and macrocycle B will be coupled using a sulfone alkylation reaction inspired by Ley's work. Syntheses of the individual optically pure fragments are based on reliable and established methods. The overall synthetic route is convergent and is well suited for the preparation of analogs.